Using techniques developed in our laboratories we will extend our observation, made for the first time, that at least one chemical carcinogen (4-nitroquinoline-1-oxide) is capable of transforming normal cells from human liver to malignant cells in vitro. A second objective of this research is to exploit techniques, also developed here, in which it is possible to enucleate mass cultures of normal and malignant human and animal cells using Cytochalasin B and centrifugation and then to fuse these anucleate cells ("cytoplasts") to whole cells with Sendai virus. The cytoplast/whole cell hybridization ("heteroplasmons") will be made between normal and malignant human and animal cells both within and between species. In addition, released nuclei will be inserted into cytoplasts by recently devised techniques, thus allowing for reconstruction experiments in which whole cells can be formed from the nucleus and cytoplasm of normal and malignant human and animal cells. The almost limitless number of permutations and combinations will allow us to answer questions bearing on (1) the role of cytoplasm and nucleus in human malignancy, (2) the fate of HL-A specificities, (3) the expression of oncogenic viral genomes, (4) the control of transformation and (5) the creation and study of cell types containing the nucleus of one cell species and the cytoplasm of another.